title: Plasma concentrations of laudanosine, but not of atracurium, are increased during the anhepatic phase of orthotopic liver transplantation in pigs.
abstract: To quantify the changes in plasma concentrations of atracurium and laudanosine induced by the lack of hepatic function and circulation, the authors studied nine domestic pigs (22-25 kg) undergoing an orthotopic liver transplantation, and three control animals without surgery, using atracurium as the muscle relaxant. After intubation facilitated by isoflurane 2-3%, anesthesia was maintained with isoflurane (0.5% in oxygen) and fentanyl (4 micrograms.kg-1.hr-1). Ventilation was controlled to keep end-tidal CO2 at 35-40 mmHg, body temperature maintained at 35.5-37.5 degrees C, and arterial pH at 7.35-7.50. The right sciatic nerve was stimulated with a nerve stimulator delivering a single twitch at 0.1 Hz with 0.2-ms duration, at supramaximal stimulation. The force of the corresponding evoked isometric muscle contraction was continuously measured by a force-displacement transducer. A single iv bolus of atracurium (2 mg/kg) was given to obtain a 90-95% twitch depression, followed 5 min later by a constant-rate iv infusion of atracurium at 120 micrograms.kg-1.min-1 maintained during the entire investigation. Blood samples for plasma atracurium and laudanosine concentrations were drawn every 15 min. In the control group, plasma concentrations of atracurium remained stable between 6.5-8.0 micrograms/ml following initial bolus injection; plasma concentrations of laudanosine increased during the first 60 min, then remained stable between 0.69-0.74 micrograms/ml up to the end of the study. In animals undergoing transplantation, plasma concentrations of atracurium remained stable between 10-12 micrograms/ml, despite a 90-min duration of liver exclusion.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery and Anesthesiology, University Medical Center, Geneva, Switzerland.
authors.forename: J F
authors.initials: JF
authors.lastname: Pittet
authors.forename: E
authors.initials: E
authors.lastname: Tassonyi
authors.forename: C
authors.initials: C
authors.lastname: Schopfer
authors.forename: D R
authors.initials: DR
authors.lastname: Morel
authors.forename: G
authors.initials: G
authors.lastname: Mentha
authors.forename: M
authors.initials: M
authors.lastname: Fathi
authors.forename: C
authors.initials: C
authors.lastname: Le Coultre
authors.forename: D A
authors.initials: DA
authors.lastname: Steinig
authors.forename: A
authors.initials: A
authors.lastname: Benakis
mesh_terms: D000818:Animals; D001279:Atracurium / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D007546:Isoquinolines / Q000097:blood*; D008099:Liver / Q000502:physiology*; D016031:Liver Transplantation / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood; D013552:Swine
chemical_list: D007546:Isoquinolines; D001279:Atracurium; C001522:laudanosine; D009638:Norepinephrine